Drug delivery classically has been via oral dosage forms that release the drug as they dissolve in the gastrointestinal tract. These delivery systems typically provide for rapid release of the active substance, which leads to the presence of maximal concentrations of the drug in the blood followed by a rapid decrease in concentration as the drug is metabolized and cleared. At these maximal concentrations, many drugs are highly toxic. Furthermore, if the concentration decreases rapidly in the body, then the time during which there is a therapeutically-effective level is short, and therapeutic efficacy requires administration of multiple doses. In addition, if release of a substance in the body cannot be controlled, then it may not be effectively delivered to the site of the body requiring treatment.
Other solutes also benefit from devices that allow for their sustained release. For example, dosing of swimming pools with chlorine or hot tubs with bromine as anti-microbial agents currently requires adding these substances to the water on a fairly regular basis. Furthermore, if the concentration is not controlled and becomes too high upon addition, then the water may not be safe or pleasant for bathers until the concentration stabilizes at lower values. Other uses for sustained-release delivery systems include, for example, delivery of food or insecticides to plants, delivery of vaccines, antibiotics, anti-parasitic agents, growth promotants or other drugs to livestock, delivery of sanitizing agents or perfumes to toilets or septic tanks, delivery antibiotics or other drugs to companion animals, delivery of dyes, bleaches or other substances in the processing of textiles, delivery of algicides to water towers or ponds, delivery of food to fish in aquaria or ponds, and delivery of any substance requiring constant delivery in an industrial manufacturing process.
Various sustained release delivery devices have been described, including those in which a solute is contained within an impermeable housing with one or more openings from which solute egresses by diffusion. Such devices purport to deliver solute at a constant (zero-order) rate; however, many deviate significantly from zero order or linear delivery. In addition, such devices often are limited in the amount of total dose deliverable, as well as by fixed parameters that make it difficult or impossible to adjust the delivery kinetics. A common feature of such prior art devices is that their release kinetics are characterized by an initial burst of solute release prior to a period of relatively constant rate of release, and the relatively constant rate of release often only crudely approximates zero order. For several reasons, such an initial burst is undesirable, as it temporarily delivers a dose in excess of the desired, effective dose, thus wasting solute, and moreover, may deliver an amount of solute which is toxic or otherwise damaging in the particular application. In addition, the initial release of a large amount of solute reduces the total amount of solute subsequently available for prolonged release by the device, thus shortening the duration of relative constant delivery, reducing its effective life and requiring more frequent replacement.
The devices and methods of the present invention overcome the disadvantages of current devices and methods for the delivery of solutes by providing for reliable and adjustable sustained release of solutes in aqueous and non-aqueous environments. In addition to exhibiting adjustable, nearly-constant release rates over suitably prolonged periods of time, the devices and methods of the invention provide for modulation or suppression of the aforementioned initial burst. The devices and methods of the invention may be applied to any of the prior-art devices relying on a fenestration or orifice and a fluid- and solute-impervious coating, to provide prolonged and near zero-order release.
Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.